MTHFR基因多态性对低剂量甲氨蝶呤单药治疗低危妊娠滋养细胞肿瘤疗效与药品不良反应的影响

Effects of MTHFR Gene Polymorphism on the Efficacy and Adverse Drug Reactions of Low-Dose Methotrexate Monotherapy for Low-Risk Gestational Trophoblastic Neoplasia

目的探讨亚甲基四氢叶酸还原酶(MTHFR)中C677T位点和A1298C位点基因型对低剂量甲氨蝶呤(MTX)单药治疗低危妊娠滋养细胞肿瘤(LR-GTN)的疗效与药品不良反应(ADR)的影响。方法收集安徽省立医院2017年9月至2021年9月收治的行MTX单药化学药物治疗(简称化疗)的LR-GTN患者30例,治疗前采集患者DNA并对MTHFR中C677T位点和A1298C位点基因多态性进行检测,分析MTHFR酶活性和各基因型对MTX疗效和ADR的影响。结果MTHFR不同的酶活性组(包括25%,48%,61%,66%,83%,100%酶活性组)MTX疗效无显著差异,MTHFR C677T位点(包括CT型、CC型、TT型)及A1298C位点(AA型、AC型、CC型)的不同基因型间MTX疗效无显著差异(P>0.05)。ADR发生率排名前3的为骨髓抑制(23例,76.67%),口腔黏膜炎(17例,56.67%),肝损伤(16例,53.33%),MTHFR不同的酶活性组间的骨髓抑制、口腔黏膜炎和肝损伤ADR的发生率无显著差异(P>0.05);MTHFR C677T及A1298C双位点不同基因型间上述ADR的发生率无显著差异(P>0.05)。结论MTHFR中C677T位点和A1298C位点基因多态性对低剂量MTX在治疗LR-GTN中的疗效与ADR未产生显著影响,但仍需进一步扩大样本量进行验证。

Objective To investigate the effects of C677T and A1298C genotypes in methylenetetrahydrofolate reductase(MTHFR)on the efficacy and adverse drug reactions(ADRs)of low-dose methotrexate(MTX)monotherapy for low-risk gestational trophoblastic neoplasia(LR-GTN).Methods Thirty LR-GTN patients treated with MTX single drug chemotherapy in the Anhui Provincial Hospital from September 2017 to September 2021 were collected.Before treatment,the patients'DNA was collected to detect the C677T and A1298C gene polymorphisms in MTHFR.The effects of MTHFR enzyme activity and each genotype on the efficacy and ADRs of MTX monotherapy for LR-GTN were analyzed.Results The efficacy of MTX monotherapy for LR-GTN among groups with different activities of MTHFR(including groups with 25%,48%,61%,66%,83%and 100%enzyme activities)was similar(P>0.05).The efficacy of MTX monotherapy for LR-GTN between different genotypes of MTHFR C677T(including CT type,CC type,TT type)and A1298C(AA type,AC type,CC type)was similar(P>0.05).The incidence of ADRs was highest in the bone marrow suppression(23 cases,76.67%),followed by oral mucositis(17 cases,56.67%)and liver injury(16 cases,53.33%).The incidence of bone marrow suppression,oral mucositis and liver injury among groups with different activities of MTHFR was similar(P>0.05).The incidence of the above three ADRs between different genotypes of MTHFR C677T and A1298C was similar(P>0.05).Conclusion The C677T and A1298C gene polymorphisms in MTHFR had no significant effect on the efficacy and ADRs of low-dose MTX monotherapy for LR-GTN,but further expansion of sample size is still needed for verification.